On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides
| Autor: | Cristian Privat, Francesc Mas, Sergio Madurga, Jaime Rubio-Martinez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Work (thermodynamics)
Polymers and Plastics Protonation constant pH molecular dynamics Tripeptide Molecular dynamics Space (mathematics) 01 natural sciences Article lcsh:QD241-441 blocked tripeptides 03 medical and health sciences Partial charge Deprotonation lcsh:Organic chemistry Equilibri àcid-base 0103 physical sciences Ramachandran maps Dinàmica molecular 030304 developmental biology 0303 health sciences 010304 chemical physics Chemistry General Chemistry Acid-base equilibrium Chemical physics Pèptids Peptides Constant (mathematics) AMBER |
| Zdroj: | Polymers Volume 13 Issue 1 Dipòsit Digital de la UB Universidad de Barcelona Polymers, Vol 13, Iss 99, p 99 (2021) |
| ISSN: | 2073-4360 |
| DOI: | 10.3390/polym13010099 |
| Popis: | Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations. |
| Databáze: | OpenAIRE |
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